U.S. Pat. No. 4,361,559 to Varma discloses antiinflammatory 17,17-bis(substituted thio)androstenes of the formula ##STR1## wherein R.sub.1 and R.sub.2 are the same or different and each is alkyl, cycloalkyl or aryl;
R.sub.3 is hydrogen, hydroxy, alkoxy, aryloxy, alkylthio, arylthio, ##STR2## or halogen; R.sub.4 is hydrogen, methyl, hydroxy, ##STR3## or halogen; R.sub.5 is hydrogen or halogen; and PA1 R.sub.6 is carbonyl or B-hydroxymethylene. A broken line in the 1,2-,6,7- and 15,16-position of a structural formula indicates the optional presence of ethylenic unsaturation.
Includes among the compounds covered in the Varma patent is tipredane which has been found to be a highly effective topical antiinflammatory agent.
Tipredane is practically insoluble in water (less than 0.0002 mg/ml at 25.degree. C.); 1:1 hydroalcoholic mixtures of tipredane are stable at pH 6.5-8.0 and unstable under acidic conditions while tipredane itself is susceptible to oxidation.
It is known to use monoglycerides such as glyceryl monostearate as a thickener in steroid cream formulations. For example, U.S. Patent No. 3,892,857 to DiFazio et al discloses a cream formulation containing propylene glycol, water and a steroid, namely, 21-chloro-9.alpha.-fluoro-.DELTA..sup.4 -pregnene-11.beta., 16.alpha., 17.alpha.-triol-3,20-dione 16,17-acetonide (halcinonide) and as an oleaginous thickener monoglycerides such as glyceryl monostearate, glyceryl monooleate, glyceryl monopalmitate and glyceryl ricinoleate.
Where it has been attempted to employ generally commercially available glyceryl monostearate in an oil-in-water tipredane cream formulation, it has been found that syneresis of the aqueous phase occurs with some lots of glycyl monostearate.
U.S. application Ser. No. 120,278, filed Nov. 13, 1987, assigned to E. R. Squibb & Sons, Inc., which will issue as U.S. Pat. No. 4,868,169 on Sept. 9, 1989, discloses a tipredane cream formulation which includes tipredane, water, an emulsifier which includes glyceryl monostearate, a buffer, a non-acid long chain fatty acid wax, optionally one or more emollients, optionally one or more chelating agents, optionally one or more lubricants, optionally one or more antioxidants, and optionally one or more skin conditioners.